Design of a Phase 1/2 Trial of Intracoronary Administration of AAV1/SERCA2a in Patients With Heart Failure

Abstract Background Heart failure (HF) remains a major cause of morbidity and mortality in North America. With an aging population and an unmet clinical need by current pharmacologic and device-related therapeutic strategies, novel treatment options for HF are being explored. One such promising stra...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cardiac failure 2008-06, Vol.14 (5), p.355-367
Main Authors: Hajjar, Roger J., MD, Zsebo, Krisztina, PhD, Deckelbaum, Lawrence, Thompson, Craig, MD, Rudy, Jeff, MD, Yaroshinsky, Alex, PhD, Ly, Hung, MD, Kawase, Yoshiaki, MD, Wagner, Kim, MA, Borow, Kenneth, MD, Jaski, Brian, MD, London, Barry, MD, Greenberg, Barry, MD, Pauly, Daniel F., MD, Patten, Richard, MD, Starling, Randall, MD, Mancini, Donna, MD, Jessup, Mariell, MD
Format: Article
Language:English
Subjects:
adeno-associated vector
Adolescent
Adrenergic beta-Antagonists - therapeutic use
Adult
Aged
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Cardiovascular
Combined Modality Therapy
Coronary Vessels
Dependovirus
Diuretics - therapeutic use
Double-Blind Method
Drug Therapy, Combination
Female
Gene therapy
Genetic Therapy
Genetic Vectors
Green Fluorescent Proteins
heart failure
Heart Failure - drug therapy
Heart Failure - enzymology
Heart Failure - genetics
Heart Failure - therapy
Humans
Male
Middle Aged
Receptors, Angiotensin - agonists
sarcoplasmic reticulum calcium ATPase
Sarcoplasmic Reticulum Calcium-Transporting ATPases - administration & dosage
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
Transduction, Genetic - methods
Transgenes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Heart failure (HF) remains a major cause of morbidity and mortality in North America. With an aging population and an unmet clinical need by current pharmacologic and device-related therapeutic strategies, novel treatment options for HF are being explored. One such promising strategy is gene therapy to target underlying molecular anomalies in the dysfunctional cardiomyocyte. Prior animal and human studies have documented decreased expression of SERCA2a, a major cardiac calcium cycling protein, as a major defect found in HF. Methods and Results We hypothesize that increasing the activity of SERCA2a in patients with moderate to severe HF will improve their cardiac function, disease status, and quality of life. Gene transfer of SERCA2a will be performed via an adeno-associated viral (AAV) vector, derived from a nonpathogenic virus with long-term transgene expression as well as a clinically established favorable safety profile. Conclusions We describe the design of a phase 1 clinical trial of antegrade epicardial coronary artery infusion (AECAI) administration of AAVI/SERCA2a (MYDICAR) to subjects with HF divided into 2 stages: in Stage 1, subjects will be assigned open-label MYDICAR in one of up to 4 sequential dose escalation cohorts; in Stage 2, subjects will be randomized in parallel to 2 or 3 doses of MYDICAR or placebo in a double-blinded manner.
ISSN:1071-9164
1532-8414
DOI:10.1016/j.cardfail.2008.02.005